Chapter 4: The Action Potential 高毓儒 Institute of Physiology, School of Medicine National Yang-Ming University Neuroscience

Outline  Introduction  Properties of the action potential  The action potential – in theory  The action potential – in reality  Action potential conduction  Action potential, axons, and dendrites  Review

Introduction Action Potential  Action potential vs. electricity  Electrical charge of ions vs. generator  Non-degraded vs. degraded conduction  All-or-none vs. adjustable characteristic  Encoding by frequency and pattern vs. magnitude of electrical power

AP-Properties Measurement

AP-Properties The Up and Down

Generation AP-Properties

 Concept of threshold  Concept of all-or-none AP-Properties

Generation  Absolute refractory period  Relative refractory period AP-Properties

AP-in Theory Current and Conductance  A simplified model at resting state ( mV)

AP-in Theory Current and Conductance  A simplified model - upon stimulation (-80 – 62 mV)

AP-in Theory Current and Conductance  A simplified model upon stimulation ( mV)

AP-in Reality Voltage-Gated Na Channel  Structure – 4 domains +

AP-in Reality Voltage-Gated Na Channel  Structure – 6 helices for each domain +

AP-in Reality Voltage-Gated Na Channel  Structure – domains for specificities +

AP-in Reality Voltage-Gated Na Channel  Depolarization and pore opening +

AP-in Reality Voltage-Gated Na Channel  Pore selectivity +

AP-in Reality Voltage-Gated Na Channel  Patch-clamp technique +

AP-in Reality Voltage-Gated Na Channel  Functional properties +

AP-in Reality Voltage-Gated Na Channel  Functional properties +

AP-in Reality Voltage-Gated Na Channel  Open with little delay.  Stay open for only 1 ms and then close (inactivate).  Cannot be opened again by depolarization until the membrane potential returns to a negative value near threshold.  The overshoot is limited by inactivation. + Characteristics

AP-in Reality Voltage-Gated Na Channel  Opining a single channel does not result in action potential.  The membrane of axon contains thousands of Na channel per  m.  Concerted action within 1 ms explains the rapidly rising phase of action potential.  Inactivation of Na channel accounts for the absolute refractory period. + Reminders +2 +

AP-in Reality Voltage-Gated Na Channel  Effect of TTX and Saxitoxin – channel blocker + Toxins

AP-in Reality Voltage-Gated Na Channel  Batrachotoxin (Frog) – lower the threshold and stay open  Toxins from Lilies and Buttercups + Toxins

AP-in Reality Voltage-Gated K Channel  Inactivation of Na channels (the 1st factor)  A transient increase in K conductance  Also open in response to depolarization with 1 ms delay - delay rectifiers (the 2nd factor)  Na -K pump working in the background at all time (the 3rd factor) + Repolarization

AP-in Reality Overall Changes in Ionic Currents

AP-in Reality Overall Changes in Ionic Currents

AP-in Reality Overall Changes in Ionic Currents

AP Conduction Propagation  Orthodromic conduction (10 m/s)  Mechanism of all-or-none Characteristics

AP Conduction  Only one direction and no turning back  Influenced by axonal size and number of voltage-gated channels  Axonal excitability  Local anesthetics Propagation Characteristics

AP Conduction Myelin and Saltatory Conduction  Insulation by myelin

AP Conduction Myelin and Saltatory Conduction  Break of insulation for ionic currents to generate AP

AP, Axons and Dendrites Difference  The membrane of dendrites and cell bodies do not have enough voltage-gated sodium channels.  They do not generate AP.  The spike-initiation zone (axonal hillock) fires the first AP.

AP, Axons and Dendrites Difference

Action Potential Review  Define membrane potential, Na equilibrium potential. Which of these, if any, changes during the course of an action potential?  What ions carry the early inward and late outward currents during the action potential?  Why is the action potential referred to as “all-or- none”? +

Action Potential Review  Some voltage-gated K are known as delay rectifiers. What would happen if these channels took much longer than normal to open?  What parts of the cell would you see the labeling of TTX? What would be the consequence?  How does action potential conduction velocity vary with axonal diameter? Why? +